Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with the genetics, genomics, and the environmental influence in causality of PCa, not many studies employing the next generation sequencing (NGS) approaches of PCa have been carried out. In our previous study, we have identified some causal genes and mutations specific to Indian PCa using Whole-Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify DEGs as well as long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened 6 patients who underwent prostatectomy; we performed a whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz. GeneMANIA Stringdb, Cytoscape-Cytohubba, cbioportal to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, HN1L and some other important genes known to be involved in different cancer pathways such as, COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1 etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, and ENST00000647843.1 that need to be characterized further. Deregulation of SOX2OT is observed in various tumors, including lung cancer, gastric cancer, esophageal cancer, breast cancer, hepatocellular carcinoma, ovarian cancer, pancreatic, laryngeal squamous cell carcinoma, osteosarcoma, nasopharyngeal carcinoma, and glioblastoma. It would be interesting to characterize its function in PCa as well. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which have perhaps not been reported. As a pilot study, this has set a precedent for us to validate further experimentally, and we firmly believe this will pave a way towards discovery of biomarkers and development of novel therapies.

Genes that affect adaptive traits have been identified, but our knowledge of the genetic basis of adaptation in a more general sense (across multiple traits) remains limited. We combined population-genomic analyses of evolve and resequence experiments, genome-wide association mapping of performance traits, and analyses of gene expression to fill this knowledge gap, and shed light on the genomics of adaptation to a marginal host (lentil) by the seed beetle Callosobruchus maculatus. Using population-genomic approaches, we detected modest parallelism in allele frequency change across replicate lines during adaptation to lentil. Mapping populations derived from each lentil-adapted line revealed a polygenic basis for two host-specific performance traits (weight and development time), which had low to modest heritabilities. We found less evidence of parallelism in genotype-phenotype associations across these lines than in allele frequency changes during the experiments. Differential gene expression caused by differences in recent evolutionary history exceeded that caused by immediate rearing host. Together, the three genomic data sets suggest that genes affecting traits other than weight and development time are likely to be the main causes of parallel evolution, and that detoxification genes (especially cytochrome P450s and beta-glucosidase) could be especially important for colonization of lentil by C. maculatus.

At the molecular level, response to an external factor or an internal condition causes reprogramming of temporal and spatial transcription. When an organism undergoes physiological and/or morphological changes, several signaling pathways are activated simultaneously. Examples of such complex reactions are the response to temperature changes, dehydration, various biologically active substances, and others. Synergistic action of multiple pathways greatly complicates the experimental study of the molecular genetic mechanisms of the organism's reactions. As a result, a significant part of the regulatory ensemble in such complex reactions remains unidentified. We developed metaRE, an R package for the systematic search for cis-regulatory elements enriched in the promoters of the genes significantly changed their transcription in a complex reaction. metaRE mines multiple expression profiling datasets generated to test the same organism's response and identifies simple and composite cis-regulatory elements systematically associated with differential expression of genes. Here we showed metaRE performance for identification of cold stress-responsive cis-regulatory code in Arabidopsis thaliana. MetaRE identified potential binding sites for known as well as unknown cold response regulators. Software with source files, documentation, and example data files are freely available online at the repository (https://github.com/cheburechko/MetaRE).

Rhodovulum spp. are anoxygenic photosynthetic purple bacteria with versatile metabolisms, including the ability to obtain electrons from minerals in their environment to drive photosynthesis, a relatively novel process called phototrophic extracellular electron uptake (pEEU). Recently, our group isolated 15 strains of R. sulfidophilum to observe this metabolism in marine phototrophs. Our group previously observed carbon dioxide fixation coupled to phototrophic iron oxidation (photoferrotrophy) and pEEU in AB26 and identified a novel di-heme c¬-type cytochrome EeuP important for pEEU but not photoferrotrophy. Taxonomic re-evaluation based on 16S and pufM phylogenetic analyses led us to re-classify two isolates, AB26 and AB19, as Rhodovulum visakhapatnamense. The AB26 genome consists of 4,380,746 base-pairs, including two plasmids, and encodes 4,296 predicted protein-coding genes. AB26 contains 22 histidine kinases, 20 response regulators, and dedicates ~16% of its genome to transport. Transcriptomic data under aerobic, photoheterotrophy, photoautotrophy, and pEEU reveals how gene expression varies between metabolisms. Lastly, we use transcriptomic data for a comparative genomic analysis of potential pEEU-relevant genes between all 15 isolates. With these data we identify potential pEEU capable phototrophs within these isolates, and likely molecular mechanisms of pEEU.

Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, which involve DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies are increasing our understanding of the epigenetic role of leukemogenesis and have demonstrated the potential of DNA methylations and histone modifications as a biomarker for lineage and subtypes classification, predicting relapse, and disease progression in ALL. Epigenetic abnormalities are relatively reversible when treated with some small molecule-based agents compared to genetic alterations. In this review, we conclude the genetic and epigenetic characteristics in ALL and discuss the future role of DNA methylation and histone modifications in predicting relapse, finally focus on the individual and precision therapy targeting epigenetic alterations.

Osteopetrosis is a group of rare inheritable disorders of the skeleton characterized by increased bone density. The disease is remarkably heterogeneous in clinical presentation and often misdiagnosed. Therefore, genetic testing and molecular pathogenicity analysis are essential for precise diagnosis and new targets for preventive pharmacotherapy. Mutations in the CLCN7 gene give rise to the complete spectrum of osteopetrosis phenotypes and are responsible for about 75% of cases of autosomal dominant osteopetrosis. In this study, we report the identification of a novel variant in the CLCN7 gene in a patient diagnosed with osteopetrosis and provide evidence for its significance (likely deleterious) based on extensive comparative genomics, protein sequence and structure analysis. A set of automated bioinformatics tools used to predict consequences of this variant identified it as deleterious or pathogenic. Structure analysis revealed that the variant is located at the same “hot spot” as the most common CLCN7 mutations causing osteopetrosis. Deep phylogenetic reconstruction showed that not only Leu614Arg, but any non-aliphatic substitutions in this position are evolutionarily intolerant, further supporting the deleterious nature of the variant. The present study provides further evidence that reconstructing a precise evolutionary history of a gene helps predicting phenotypical consequences of variants of uncertain significance.

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.

Members of the insect ATP binding cassette transporter subfamily C2 (ABCC2) in several moth species are known as receptors for the Cry1Ac insecticidal protein from Bacillus thuringiensis (Bt). Mutations that abolish the functional domains of ABCC2 are known to cause resistance to Cry1Ac, although the reported levels of resistance vary widely depending on insect species. In this study, the function of the ABCC2 gene as putative Cry1Ac receptor in Helicoverpa zea, a major pest of over 300 crops, was evaluated using CRISPR/Cas9 to progressively eliminate different functional ABCC2 domains. Results from bioassays with edited insect lines support that muta-tions in ABCC2 was associated with Cry1Ac resistance ratios (RR) ranging from 7.3- to 39.8-fold. No significant differences in susceptibility to Cry1Ac were detected between H. zea with partial or complete ABCC2 knockout, although highest levels of tolerance were observed when knocking out half of ABCC2. Based on >500-1,000-fold RRs reported in similar studies for closely related moth species, the low RRs observed in H. zea knockouts support that ABCC2 is not a major Cry1Ac receptor in this insect.

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease and/or mycotoxin contamination on numerous crops. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport, through to virulence/pathogenicity. Most emerged early during the evolution of Fusarium/FFSC and were subsequently retained only in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in grass- and pine-associated FFSC taxa examined and highlighted the diversity of molecular processes potentially underlying niche-specificity in these and other Fusarium species.

Dissolved organic matter (DOM) in the ocean represents about 662 billion tonnes of C, 200 times more than the living biomass. It is produced mainly by microbial primary production. The largest fraction of this DOM is old (>weeks to months) and both chemically and biologically recalcitrant. The remainder is young (seconds to weeks), more labile and surface active. It also changes the rheological properties in the bulk phase of the water and at interfaces including the sea surface microlayer (SML). In order of abundance, this DOM consists of sugars, amino acids, fatty acids and nucleic acids, often incorporated into complex polymers. The DOM molecules are produced by microbial genes, and are further modified by enzymes themselves produced by genes. The properties of ocean water and its interfaces as well as biogeochemical fluxes may thus be modified by ocean microbial genes. These fluxes influence ocean and atmospheric climate, which in return acts on the biota. Therefore the ocean microbial genomes and the fluxes and climates they influence may be subject to Darwinian-type selection. Research programmes need to integrate ocean ecology, rheology, biogeochemistry and genomics, to find the associations among them. Discovery of commercial bioactive molecules may be a bonus.

Genomics has put prokaryotic rank-based taxonomy on a solid phylogenetic foundation. However, most taxonomic ranks were set long before the advent of DNA sequencing and genomics. In this concept paper, we thus ask the simple yet profound question: Should prokaryotic classification schemes besides the current phylum-to-species ranks be explored, developed, and incorporated into scientific discourse? Could such alternative schemes provide better solutions to the basic need of science and society for which taxonomy was developed, namely, precise and meaningful identification? A neutral genome-similarity based framework is then described that could allow alternative classification schemes to be explored, compared, and translated into each other without having to choose only one as the gold standard. Classification schemes could thus continue to evolve and be selected according to their benefits and based on how well they fulfill the need for prokaryotic identification.

The comparative phylogeography of marine species with contrasting dispersal potential across the southern Caribbean Sea was evaluated by the presence of two putative barriers: the Magdale-na River plume (MRP) and the combination of the absence of a rocky bottom and permanent upwelling in the La Guajira Peninsula (ARB+PUG). Three species of rocky shallow bottoms were selected with different dispersal potentials: Acanthemblemaria rivasi (PLD < 22 days), Cittarium pica (PLD < 6 days), and Nerita tessellata (PLD > 60 days). We generated a set of SNPs for the three species using the ddRad-seq technique. Samples of each species were collected in five locations from Capurganá to La Guajira. For the first time, evidence of a phylogeographic break caused by MRP is provided, mainly for A. rivasi (AMOVA: ФCT = 0.420). The ARB+PUG barrier causes an-other break for A. rivasi (ФCT = 0.406) and C. pica (ФCT = 0.224). Three populations (K = 3) were identified for A. rivasi and C. pica, while N. tessellata presented one population (K = 1). The Mantel correlogram indicated that A. rivasi and C. pica fit the hierarchical population model, and only the A. rivasi and C. pica comparisons showed phylogeographic congruence. Our results demon-strate how the biological traits of these three species and the biogeographic barriers have influ-enced their phylogeographic structure.

Capirona (Calycophyllum spruceanum Benth.) belongs to subfamily Ixoroideae, one of de major lineages in the Rubiaceae family, and is an important timber tree, with origin in the Amazon Basin and has widespread distribution in Bolivia, Peru, Colombia, and Brazil. In this study, we obtained the first complete chloroplast (cp) genome of capirona from department of Madre de Dios located in the Peruvian Amazon. High-quality genomic DNA was used to construct librar-ies. Pair-end clean reads were obtained by PE 150 library and the Illumina HiSeq 2500 platform. The complete cp genome of C. spruceanum has a 154,480 bp in length with typical quadripartite structure, containing a large single copy (LSC) region (84,813 bp) and a small single-copy (SSC) region (18,101 bp), separated by two inverted repeat (IR) regions (25,783 bp). The annotation of C. spruceanum cp genome predicted 87 protein-coding genes (CDS), 8 ribosomal RNA (rRNA) genes, 37 transfer RNA (tRNA) genes and 01 pseudogene. A total of 41 simple sequence repeats (SSR) of this cp genome were divided into mononucleotides (29), dinucleotides (5), trinucleotides (3), and tetranucleotide (4). Most of these repeats were distributed in the noncoding regions. Whole chloroplast genome comparison with the other six Ixoroideae species revealed that the small single copy and large single copy regions showed more divergence than invert regions. Finally, phylogenetic analysis resolved that C. spruceanum is a sister species to Emmenopterys henryi, and confirms its position within the subfamily Ixoroideae. This study reports for the first time the genome organization, gene content, and structural features of the chloroplast genome of C. spruceanum, providing valuable information for genetic and evolutionary studies in the genus Calycophyllum and beyond.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

Breast cancer has an important incidence in the worldwide female population. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. The purpose of the present work was to explore mitochondrial sequences of clinical cases with breast cancer from different origins and determine the polymorphisms associated. The search for complete and partial mtDNA sequences obtained from breast cancer patients and controls was performed in NCBI Genbank database. We identified 124 mtDNA sequences associated to breast cancer cases of which 86 were complete and 38 partial sequences. Of these 86 complete sequences, 52 belong to patients with a confirmed diagnosis of breast cancer and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls. From mtDNA analysis, two polymorphisms with significative statistical differences were found in D130 in sequences analyzed: m.310del (rs869289246) in 34.6% (27/78) breast cancer cases and 61.7% (21/34) of controls; and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) of controls. Also, the variant m.16519T>C (rs3937033) was found in 59% of control sequences and 52% of breast cancer sequences with a significant statistical difference. Polymorphic changes are evolutionarily related to haplogroup H of Indo-European and Euro Asiatic origins, however, were found in all non-European sequences with breast cancer.

Targeting genes involved in sexual determinism for vector or pest control purpose, requires a better understanding of their polymorphism in natural populations in order to ensure a rapid spread of the construct. By using genomic data from An. gambiae s.l., we analyzed the genetic variation and the conservation score of the fru gene in 18 natural populations across Africa. A total of 34339 SNPs were identified including 3.11% non-synonymous segregating sites. Overall, the nucleotide diversity was low and the Tajima's D neutrality test was negative indicating an excess of low frequency SNPs in the fru gene. The allelic frequencies of the non-synonymous SNPs were low (freq < 0.26) except two SNPs identified at high frequencies (freq > 0.8) in the Zinc-finger A and B protein domains. The conservation score was variable throughout the fru gene with maximum values in the exonic compared to the intronic regions. These results showed a low genetic variation in overall the exonic regions especially the male sex-specific exon and the BTB-exon 1 of the fru gene. These findings are crucial for the development of a gene drive construct targeting the fru gene that can rapidly spread without encountering resistance in wild populations.

Hearing loss stands as the most prevalent sensory deficit among humans, posing a significant global health challenge. Projections indicate that by 2050, approximately 10% of the world's population will grapple with disabling hearing impairment. While approximately half of these cases have a genetic etiology, traditional interventions such as hearing aids and cochlear implants do not completely restore normal hearing. The absence of biological treatment has prompted significant efforts in recent years, with a strong focus on gene therapy to address hereditary hearing loss. Although several studies have exhibited promising recovery of common forms of genetic deafness in mouse models, existing challenges must be overcome to make gene therapy applicable in the near future. Herein, we summarize the primary gene therapy strategies employed over past years, provide an overview of the recent achievements in the preclinical studies for genetic hearing loss, and outline the current key obstacles to cochlear gene therapy.

As commonly used chemical plasticizers in plastic products, phthalate esters had become a serious ubiquitous environmental pollutant, such as in soil of plastic film mulch culture. Microbial degradation or transformation was regarded as a suitable strategy to solve the phthalate esters pollution. Thus, a new phthalate esters degrading strain Gordonia sp. GZ-YC7 was isolated in this study, which exhibited the highest di-(2-ethylhexyl) phthalate degradation efficiency under 1000 mg/L and the strongest tolerance to 4000 mg/L. The comparative genomic analysis showed that there exist diverse degradation pathways for various phthalate esters such as di-(2-ethylhexyl) phthalate and dibutyl phthalate in Gordonia sp. GZ-YC7, which possibly contributes to its broad substrate spectrum, high degrading efficiency and high tolerance to phthalate esters. Gordonia sp. GZ-YC7 is potential for bioremediation of phthalate esters in polluted soil environments.

Bunyaviruses represent the largest group of RNA viruses, and are the causative agent of a variety of febrile and hemorrhagic illnesses. Originally characterized as a single serotype in Africa, the number of described bunyaviruses now exceeds over 500, with its presence detected around the world. These predominantly tri-segmented, single-stranded RNA viruses are transmitted primarily through arthropod and rodent vectors, and can infect a wide variety of animal and plants. Although encoding for a small number of proteins, these viruses can inflict potentially fatal disease outcomes, and have even developed strategies to suppress the innate antiviral immune mechanisms of the infected host. This short review will attempt to provide an overall description of the order Bunyavirales, describing the mechanisms behind their infection, replication and their evasion of the host immune response. Furthermore, the historical context of these virus will be presented, starting from their original discovery almost 80 years ago, to the most recent research pertaining to viral replication and host immune response.

Rabies is a fatal zoonosis that is considered a re-emerging infectious disease. Although rabies remains endemic in canines throughout much of the world, vaccination programs have essentially eliminated dog rabies in the Americas and much of Europe. However, despite the goal of eradicating dog rabies in the European Union by 2020, sporadic cases of dog rabies still occur in Eastern Europe, including Georgia. To assess the genetic diversity of strains recently circulating in Georgia, we sequenced 78 RABV-positive samples from brain tissues of rabid dogs and jackals using Illumina short-read sequencing of total RNA shotgun libraries. Seventy-seven RABV genomes were successfully assembled and annotated, 74 of them to the coding complete status. Phylogenetic analyses of the nucleoprotein (N) and attachment glycoprotein (G) genes placed all the assembled genomes into the Cosmopolitan clade, consistent with the Georgian origin of the samples. Amino acid alignment of the G glycoprotein ectodomain identified twelve different sequences for this domain among the samples. Only one of the ectodomain groups contained a residue change in an antigenic site, an R264H change in the G5 antigenic site. Three isolates were cultured, and these were found to be efficiently neutralized by human monoclonal antibody A6. Overall, our data show that recently circulating RABV isolates from Georgian canines are predominantly closely related phylogroup I viruses of the Cosmopolitan clade. Current rabies vaccines should offer protection against infection by Georgian canine RABVs. The genomes have been deposited in GenBank (accessions: OQ603609-OQ603685).

Snakes are a vital component of wildlife resources and are widely distributed across the globe. Bungarus multicinctus, a highly venomous snake, is found in central and southern China. B. multicinctus is a highly venomous snake and is distributed in central and southern China. Snakes are an ancient group of reptiles, and their genome resources can provide important clues for understanding the evolutionary history of reptiles. Meanwhile, genomic resources play a crucial role in comprehending the evolution of species. So far, the genomic resources of snakes are a rarity. In 2021, a snake sample was collected from Beiliu Longgukeng, Guangxi, which was identified as B. multicinctus through morphological identification. In this study, we present a highly contiguous genome of B. multicinctus with a size of 1.51 Gb. The genome contains a repeat content of 40.15%, with a total length exceeding 620 Mb. Additionally, we annotated a total of 24,869 functional genes. This research is of great significance for comprehending the evolution of B. multicinctus and provides a genomic basis for the genes involved in venom gland function.

Advanced genomics, transcriptomics and epigenomics techniques are providing unprecedented insights into the understanding of the molecular underpinnings of the central nervous system, including the neuro-sensory cochlea of the inner ear. Here, we report for the first time a comprehensive and updated overview of the most advanced omics techniques for the study of nucleic acids, and their applications in cochlear research. We describe the available in vitro and in vivo models for hearing research, the principles of genomics, transcriptomics and epigenomics, alongside their most advanced technologies (like single cell omics and spatial omics), which allows to investigate the molecular events that occur at single cell resolution retaining the spatial information.

Standardized gene nomenclature supports unambiguous communication and identification of the scientific literature associated with genes. To support the increasing number of annotated genomes that are now available for comparative studies, gene nomenclature authorities coordinate the assignment of approved gene names that can be readily propagated across species. Theofanopoulou et al. (Theofanopoulou et al. 2021) propose a new nomenclature for the genes encoding oxytocin and arginine vasopressin and their receptors. Rather than changing to a different nomenclature system, we propose minor updates to the current approved nomenclature of these vertebrate genes to better reflect their evolutionary history. We call on authors, journal editors and reviewers to help support communication and indexing of gene-related publications by working with existing gene nomenclature committees and ensuring that standardized gene nomenclature is routinely used.

A few empirical examples document fixed alternative male mating strategies in animals. Here we focus on the polymorphism of male mating strategies in the ruff (Calidris pugnax, Aves Charadriiformes). In ruffs, three fixed alternative male mating strategies coexist and are signaled by extreme plumage polymorphism. We first present relevant data on the biology of the species. Then we review the available knowledge of the behavioral ecology of ruffs during the breeding season and we detail the characteristics of each of the three known fixed male mating strategies. We next turn to the exceptional quality results accumulated on both the structural and functional genomics of the ruff over the past few years. We show how much these genomic data can shed a new, mechanistic light on the evolution and maintenance of the three fixed alternative male mating strategies. We then look if there are sufficient indication to support frequency-dependent selection as key mechanism in maintaining these three strategies. Specifically, we search for evidences of equal fitness among individuals using each of the three strategies. Finally, we propose three lines of research avenues that will help to understand the eco-evolutionary dynamics of phenotypic differences within natural populations of this iconic model species.

Dynamic variables in the non-equilibrium systems of life are determined by catalytic activities. These relate to the expression of the genome. The extent to which such a variable depends on the catalytic activity defined by a gene has become more and more important in view of the possibilities to modulate gene expression or intervene with enzyme function through the use of medicinal drugs. With all the complexity of cellular systems biology, there are still some very simple principles that guide the control of variables such as fluxes, concentrations, and half-times. Using time-unit invariance we here derive a multitude of laws governing the sums of the control coefficients that quantify the control of multiple variables by all the catalytic activities. We show that the sum of the control coefficients of any dynamic variable over all catalytic activities is determined by the control of the same property by time. When the variable is at a maximum, minimum or steady, this limits the sums to simple integers like 0, -1, 1, and -2, depending on the variable under consideration. Some of the implications for biological control are discussed as is the dependence of these results on the precise definition of control.

This review article offers an in-depth look at DNA, its discovery, structure, functions, and the significant role it plays in modern biomedical research. It begins by revisiting the landmark discovery of the DNA double helix by scientists Watson and Crick, a structure resembling a twisted ladder that forms the blueprint of life. The review explains the basic processes of DNA replication (copying DNA), transcription (converting DNA to RNA), and translation (turning RNA into proteins), which are fundamental to understanding how genetic information is passed on and used by living organisms. The article then explores gene regulation and epigenetics, which involve how genes are turned on or off and how environmental factors can affect gene expression without changing the DNA sequence itself. It examines how DNA interacts with various proteins and modifiers, which play crucial roles in these processes. A major focus is on the advancements in DNA sequencing technologies. From the initial Sanger sequencing method, which was labor-intensive and time-consuming, to the highly efficient next-generation sequencing (NGS) and the latest single-molecule sequencing techniques, the review covers how these technologies have revolutionized genomics and personalized medicine. It also highlights the importance of computational genomics and bioinformatics, fields that deal with analyzing and interpreting the vast amounts of data generated by DNA sequencing. The review discusses DNA's crucial role in understanding human diseases. It covers DNA-based research in cancer, rare genetic disorders, infectious diseases, and pharmacogenomics (how genes affect a person's response to drugs). It emphasizes studies that have led to new ways of diagnosing and treating diseases. The article looks at the future of DNA research. It talks about emerging technologies like CRISPR-Cas9, a revolutionary gene-editing tool that allows scientists to modify DNA with high precision. Synthetic biology, an interdisciplinary field that combines biology and engineering for designing and constructing new biological parts and systems, is also discussed. Furthermore, DNA nanotechnology, which involves designing DNA molecules for technological uses, is explored. Finally, the review addresses ethical issues in DNA research, such as privacy concerns and debates over genome editing.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

: Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasize, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8,332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8,332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.

Trypanosoma cruzi, the protozoan causative of Chagas disease (ChD), exhibits striking genetic and phenotypic intraspecific diversity, along with ecoepidemiological complexity. Human-pathogen interactions lead to distinct clinical presentations of ChD. In 2009, an international consensus classified T. cruzi strains into six discrete typing units (DTUs), TcI to TcVI, later including TcBat, and proposed reproducible genotyping schemes for DTU identification. This article aims to review the impact of classifying T. cruzi strains into DTUs on our understanding of biological, ecoepidemio-logical, and pathogenic aspects of T. cruzi. We will explore the likely origin of DTUs and the intrinsic characteristics of each group of strains concerning genome organization, genomics, and suscepti-bility to drugs used in ChD treatment. We will also provide an overview of the association of DTUs with mammalian reservoirs, and summarize the geographic distribution, and the clinical implica-tions, of prevalent specific DTUs in ChD patients. Throughout this review, we will emphasize the crucial roles of both parasite and human genetics in defining ChD pathogenesis and chemotherapy outcome.

In an era of unparalleled technical advancement, the pharmaceutical industry is struggling to transform data into increased research and development efficiency, and as a corollary, new drugs for patients. Here, we briefly review some of the commonly discussed issues around this counterintuitive innovation crisis. Looking at both industry and science related factors, we posit that traditional preclinical research is front-loading the development pipeline with data and drug candidates that are unlikely to succeed in patients. Applying a first principles analysis, we highlight the critical culprits and provide suggestions as to how these issues can be rectified through pursuit of a Human Data-driven Discovery (HD3) paradigm. Consistent with other examples of disruptive innovation, we propose that new levels of success are not dependent on new inventions, but rather the strategic integration of existing data and technology assets. In support of these suggestions, we highlight the power of HD3, through recently published proof-of-concept applications in the areas of drug safety analysis and prediction, drug repositioning, rational design of combination therapies and the global response to the Covid19 pandemic. We conclude that innovators must play a key role in expediting the path to a largely human focused, systems-based approach to drug discovery and research.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Habitat loss and fragmentation are of concern to conservation biologists worldwide. However, not all organisms are affected equally by these processes, thus it is important to study the effects of living in fragmented habitats on species that differ in lifestyle and habitat requirements. In this study we examined dispersal and connectivity patterns of rodents, one endemic (Eliurus myoxinus) and one invasive (Rattus rattus), in two landscapes containing forest fragments and adjacent continuous forest patches in northwestern Madagascar. We generated genomic (RADseq) data for 66 E. myoxinus and 81 R. rattus individuals to evaluate differences in genetic diversity as well as inbreeding and connectivity in two landscapes. We found higher levels of inbreeding and lower levels of genetic diversity in E. myoxinus compared with R. rattus. We observed related dyads both within and between habitat patches and positive spatial autocorrelation at lower distance classes for both species, with a stronger pattern of spatial autocorrelation in R. rattus. Across each site we identified contrasting migration rates for each species, but these did not correspond to habitat-matrix dichotomies. The relatively low genetic diversity in the endemic E. myoxinus suggests ecological constraints that require further investigation.

Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. The present study aims at scanning 70 single-point mutations on the APP gene in a publicly available genetic dataset including 2.504 healthy individuals from 26 populations, and analyzing their distribution. Moreover, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations have been detected in the worldwide dataset, with several of them being specific for a single individual, population or macroarea. Patterns of segment sharing reflect recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups, and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementias.

In response to escalating global demand for poultry, the industry grapples with an array of intricate challenges, from enhancing productivity to improving animal welfare and attenuating environmental impacts. This comprehensive review explores the transformative potential of digital phenotyping, an emergent technological innovation at the cusp of dramatically reshaping broiler production. The central aim of this study is to critically examine digital phenotyping as a pivotal solution to these multidimensional industry conundrums. Our investigation spotlights the profound implications of 'digital twins' in the burgeoning field of broiler genomics, where the production of exact digital counterparts of physical entities accelerates genomics research and its practical applications. Further, this review probes into the ongoing advancements in the research and development of a context-sensitive, multimodal digital phenotyping platform, custom-built to monitor broiler health. I critically evaluate this platform's potential in revolutionizing health monitoring, fortifying the resilience of broiler production, and fostering a harmonious balance between productivity and sustainability. Subsequently, the paper provides a rigorous assessment of the unique challenges that may surface during the integration of digital phenotyping within the industry. These span from technical and economic impediments to ethical deliberations, thus offering a comprehensive perspective. The paper concludes by highlighting the game-changing potential of digital phenotyping in the broiler industry and identifying potential future directions for the field, underlining the significance of continued research and development in unlocking digital phenotyping's full potential. In doing so, it charts a course towards a more robust, sustainable, and productive broiler industry. The insights garnered from this study hold substantial value for a broad spectrum of stakeholders in the broiler industry, setting the stage for an imminent technological evolution in poultry production.

Understanding the genetic architecture of a disease is crucial for development of valid diagnostic and therapeutic interventions. The analysis of genomic variations associated with pathological conditions is the starting point for uncovering disease-causing pathways (candidate processes). However, the complexity of intergenic and genetic-environmental interactions hinders the identification of pathogenic values of genomic changes. Furthermore, heredity, epigenetics and somatic mosaicism make the interpretation of genomic data even more sophisticated. To succeed, a variety of bioinformatic techniques are applied. Here, reviewing own and literature data, knowledge-based prioritization of genomic variations is described. Theoretical basis of the knowledge-based prioritization is given with a special regard to gene ontology, heuristics, hermeneutics (genomic hermeneutics) and analytics. Practical and methodological issues of prioritization using ontology- or pathway-based systems analysis are considered in the light of optimistic and realistic scenarios of cumulative phenotypic effects of the variome (the whole set of genomic variations in an individual or specific set of genomic variations for a phenotypic outcome). In the present communication, copy number variants (CNVs) in children with neurodevelopmental diseases are used as a practical foundation for the prioritization, inasmuch as these genome variations are systematically overlooked in the so-called NGS era. Nonetheless, it is highly likely that the prioritization is applicable to almost all types of genomic variations (e.g. chromosome abnormalities, gene mutations, functional synonymous variants etc.). The present methodology seems to be a valuable addition to current biomedical science widening the opportunities for medical genomics and genetics.

The accumulation of loss of function mutations in the uricase gene well explains the high urate levels in hominoids (apes and humans) compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in the antioxidant role of urate and the role of the uricase gene in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase gene in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.

The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

Cryptosporidiosis is a widespread disease caused by the parasitic protozoan Cryptosporidium spp., which infects various vertebrate species, including humans. Once unknown as a gastroenteritis-causing agent, Cryptosporidium spp. is now recognized as a pathogen causing life-threatening disease, especially in immunocompromised individuals such as AIDS patients. Advances in diagnostic methods and increased awareness have led to a significant shift in the perception of Cryptosporidium spp. as a pathogen. Nowadays, genomic and proteomic studies have played a main role in understanding the molecular biology of this complex-life-cycle parasite. Genomics has enabled the identification of numerous genes involved in the parasite's development and interaction with hosts. Proteomics has allowed for the identification of protein interactions, their function, structure, and cellular activity. The combination of these two approaches has significantly contributed to the development of new diagnostic tools, vaccines, and drugs for cryptosporidiosis. In this review, we summarize the major accomplishments in the field of Cryptosporidium research using genomics and proteomics.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with GWAS studies showing that many psoriasis risk genes lie along the IL23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. The pathogenesis of psoriasis is complex and focusing on the IL23/Th17 axis can provide insight into key cell types, cytokines and intracellular signaling pathways involved. Examination of currently available biological treatments, time to relapse post drug withdrawal and rates of drug primary/secondary drug failure show the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely reduce dis-ease burden for the longest period possible.

Novel genetic risk markers have helped to advance the field of cardiovascular epidemiology and refine our current understanding and risk stratification paradigms. Discovery and analysis of variants can help to tailor prognostication and management. However, populations underrepresented in cardiovascular epidemiology and cardiogenetics research may experience inequities in care if prediction tools are not applicable to them clinically. Therefore, the purpose of this article is to outline the barriers that underrepresented populations can face in participating in genetics research, describe current efforts to diversify cardiogenetics research, and outline strategies that researchers in cardiovascular epidemiology can implement to include underrepresented populations. Mistrust, a lack of diverse research teams, improper use of sensitive biodata, and constraints of genetic analyses are all barriers for including diverse populations in genetics studies. Current work is beginning to address the paucity of ethnically diverse genetics research and has already begun to shed light on the potential benefits of including underrepresented and diverse populations. Reducing barriers for individuals, utilizing community-driven research processes, adopting novel recruitment strategies, and pushing for organizational support for diverse genetics research are key steps that clinicians and researchers can take to develop equitable risk stratification tools and improve patient care.

Histone modifications, especially H3K27 and H3K36 methylations, are crucial for epigenetic regulation and are often dysregulated in cancer. In a comprehensive analysis of 11,194 patient samples across 32 cancer types, we identified significant genomic alterations in H3K27 and H3K36 modifiers, with the most common being in KDM6B, BRPF1, KDM6A, SETD2, and NSD1. Patients with these alterations also frequently exhibited mutations in genes like TP53 and PIK3CA. Moreover, the presence of these histone modifier alterations correlated with poorer overall survival, emphasizing their potential as both oncogenic drivers and prognostic markers in various cancers.

Paleogenomics focuses on the recovery, manipulation, and analysis of ancient DNA (aDNA) from historical or long-dead organisms to reconstruct and analyze their genomes. The aDNA is commonly obtained from remains found in paleontological and archaeological sites, conserved in museums and in other archival collections. Herbarium collections represent a great source of phenotypic and genotypic information, and their exploitation allowed to infer and to clarify previously unsolved taxonomic and systematic relationships. Moreover, Herbarium specimens offered a new source to study phenological traits in plants and to disentangle biogeography and evolutionary scenarios of species. More recently, advances in the molecular technologies went in parallel with the decreasing costs of the next-generation sequencing (NGS) approaches, that paved the way to the utilization of aDNA for whole-genome studies. Although many studies have been carried out combining modern analytic techniques and Herbarium specimens, this research field is still relatively unexplored, due to the need of improving strategies for aDNA manipulation and exploitation. The higher susceptibility of aDNA to degradation and contamination during the Herbarium conservation and manipulation, and the occurrence of biochemical post-mortem damages, can result in the more challenging reconstruction of the original DNA sequence. Here, we review the methodological approaches that have been developed for the exploitation of historical Herbarium plant materials, such as the best practices for aDNA extraction, amplification and genotyping. We also focus on some strategies to overcome the main problems related to the utilization of Herbarium specimens for their exploitation in plant evolutionary studies.

Asymmetry plays a major role in biology at all scales. This can be seen examining the helix of DNA, the fact that the human heart is on the left side, or that most people use their right hand. A single protein such as Myosin 1D can induce helical motion in another molecule. This causes cells, organs, and even entire bodies to twist in a domino effect, causing left-right behaviour. More in general, athlete movements are often asymmetric and, during the physical rehabilita-tion after injury the asymmetry is visually discernible. Herein we review the molecular basis of movement asymmetries and report on the available knowledge on the few therapeutics inves-tigated so far such as meloxicam. From a more rehabilitative perspective, it is very important to use effective methods to control the process of resolving the injury-related movement asym-metry through the complex use of specialized exercises, measurements and gait analysis which all can provide useful information on the effectiveness of rehabilitation plans. If for each athlete the normal range of asymmetry is known, the asymmetry can be treated individually and the evolution can be monitored over time. Appropriate measures should be taken if the movement asymmetry is outside this range. In addition, genetic, physiological, and psychological factors relevant to athlete health should be considered in the process of assessing and improving exer-cise asymmetry as we also discuss in this review. The main proposal of this work is that move-ment asymmetries in athletes should be treated individually, taking into account the athlete’s genetics, physical condition, and previous injuries.

Prostate cancer is a highly heterogeneous disease, and mortality is mainly due to metastases, but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor. We demonstrate that genes related to oxidative phosphorylation are upregulated in LNM and in African-American patients relative to White patients. We further show that mutations in TP53, FLT4, EYA1, NCOR2, CSMD3, and PCDH15 are enriched in prostate cancer metastases. These findings were validated in a meta-analysis of 3,929 primary tumors and 2,721 metastases and reveal a pattern of molecular alterations underlying the pathology of metastatic prostate cancer. We show that LNM contain multiple subclones that are already present in primary tumor foci. We observed enrichment of mutations in several genes including understudied genes such as EYA1, CSMD3, FLT4, NCOR2, and PCDH15 and find that mutations in EYA1 and CSMD3 are associated with poor outcome in prostate cancer.

The king ratsnake (Elaphe carinata) of the genus Elaphe is a common large non-venomous snake that is widely distributed in Southeast and East Asia, and is an economically important farmed snake species. As a non-venomous snake, the king snake that is predatory on venomous snakes such as cobras and pit vipers. The immune mechanisms of which has been unclear. Despite their economic and research importance, genomic resources which will benefit studies in toxicology, phylogeography and immunogenetics are lacking. In this study, we use single-tube long fragment read (stLFR) sequencing to display the first complete genome of a King ratsnake from Huangshan City, Anhui province in China. The genome size is 1.56GB with a scaffold N50 of 6.53M, the total length of the genome is approximately 621Mb, and the repeat content is 38.90%. Additionally, we predicted 22,339 protein-coding genes, of which 22,065 had functional annotations. Our genome is a potentially useful addition to those currently available for snakes.

Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYA) with sarcoma are a unique and under-studied patient population that have only achieved modest survival gains compared to other groups. We present our institutional experience of AYA with sarcoma who underwent comprehensive molecular profiling (CMP) using either large-panel targeted DNA sequencing or whole genome and transcriptome sequencing and evaluated the feasibility and clinical impact of this approach. Genomic variants detected were determined to be clinically relevant and actionable following the Molecular Tumour Board evaluation. Clinicians provided feedback regarding the utility of testing three months after reporting. Twenty-five patients who were recruited for CMP are included in this analysis. The median time from consent to final molecular report was 45 days (interquartile range 37-57). Potentially actionable variants were detected for 14 patients (56%) and new treatment recommendations were identified for 12 patients (48%). Pathogenic germline variants were identified in three patients (12%), and one patient had a change of diagnosis. Implementation for CMP for AYA with sarcoma is clinically valuable, feasible and should be increasingly integrated into routine clinical practice as technologies and turnaround times continue to improve.

Background: The purpose of this study is to carry out bioinformatic analysis of lncRNA data obtained as a result of genomic analysis of kidney tissue samples taken from rats with nephrotoxicity induced by methotrexate (MTX) and from rats without pathology and modeling with tree-based machine learning method. Another aim of the study is to identify potential biomarkers for the diagnosis of nephrotoxicity and to provide a better understanding of the nephrotoxicity formation process by providing the interpretability of the model with explainable artificial intelligence methods as a result of the modeling. Methods: To identify potential indicators of drug-induced nephrotoxicity, 20 female Wistar Albino rats were separated into two groups: nephrotoxicity and control. Kidney tissue samples were collected from the rats, and genomic, histological, and immunohistochemical analyses were performed. The data set obtained as a result of genomic analysis was modeled with Random Forest (RF), one of the tree-based methods. Modeling results were evaluated with sensitivity (Se), specificity (Sp), balanced accuracy (B-Acc), negative predictive value (Npv), accuracy (Acc), positive predictive value (Ppv), and F1-score performance metrics. The Local Interpretable Model-Agnostic Annotations (LIME) method was used to determine the lncRNAs that could be biomarkers for nephrotoxicity by providing the interpretability of the RF model. Results: The outcomes of the histological and immunohistochemical analyses done in the study supported the conclusion that MTX use caused kidney injury. According to the results of the bioinformatics analysis, 52 lncRNAs showed different expression in the groups. As a result of modeling with RF for lncRNAs selected with Boruta variable selection, the B-Acc, Acc, Sp, Se, Npv, Ppv, and F1-score were 88.9%, 90%, 90.9%, 88.9%, 90.9%, 88.9% and 88.9%. respectively. lncRNAs with id rnaXR_591534.3 rnaXR_005503408.1, rnaXR_005495645.1, rnaXR_001839007.2, rnaXR_005492056.1 and rna_XR_005492522.1 the lncRNAs with the highest variable importance values produced from RF modeling can be used as nephroxicity biomarker candidates. Also, according to the LIME results, the high level of lncRNAs with id rnaXR_591534.3 and rnaXR_005503408.1 especially increased the possibility of nephrotoxicity. Conclusions: With the possible biomarkers obtained as a result of the analyses made within the scope of this study, it can be ensured that the procedures for the diagnosis of drug-induced nephrotoxicity can be carried out easily, quickly and effectively.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

Trimeresurus albolabris, also known as the white-lipped pit viper or white-lipped tree viper, is a highly venomous snake distributed across Southeast Asia and the cause of many snakebite cases. In this study, we report the first whole genome assembly of T. albolabris obtained with next-generation sequencing from a specimen collected in Mengzi, Yunnan, China. After genome sequencing and assembly, the genome of this male T. albolabris individual was 1.51 Gb in length and included 38.42% repeat-element content. Using this genome, 21,695 genes were identified, and 99.17% of genes could be annotated using gene functional databases. Our genome assembly and annotation process was validated using a phylogenetic tree, which included six species and focused on single-copy genes of nuclear genomes. This research will contribute to future studies on Trimeresurus biology and the genetic basis of snake venom.

In our article in Genome Biology Ecology six years ago, one complete plastid genome of Belian was assembled for comparative analyses of the plastomes in Lauraceae. However, Ariati et al. (2023) concluded that our sequenced Belian individual could be located in the clade of Myristicaceae instead of that of Lauraceae. Here, we performed re-analyses of additional two Belian plastomes, along with 42 plastomes from plants spanning ten families of the Magnoliids. The plastomes of the three Belian individuals range from 157,535 to 157,577 bp in length. Comparative genomic analysis revealed 170 mutation sites in their plastomes, which include 111 substitutions, 53 indels, and six microinversions. Phylogeny was reconstructed using maximum likelihood and Bayesian approaches for 44 magnoliids species indicated that our three Belian individuals are nested among the species in the family Lauraceae rather than Myristicaceae.

GS provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. But there are good reasons to remain cautious about the broad implementation of these strategies in babies and children. At best, rapid GS leads to diagnoses in many infants in highly selected populations. It sometimes leads to beneficial and changes in management. Parents and physicians both often find these results useful. We don’t know how useful such testing will be in the general population. It is almost inevitable that genetic counseling will be more challenging in a more general population. We don’t know how often GS helps improve outcome and survival or reduce symptoms in babies who receive a molecular diagnosis. We don’t know the relative cost-effectiveness of whole genome, whole exome, or targeted panels in different populations. We don’t know the relative contribution of a molecular diagnosis to the decision to withdraw life support. Each of these concerns will require careful study of both the technology and the ethical issues to allow us to harness the potential of these new technologies while avoiding foreseeable problems. Studies are underway to see how the tests are used in general populations. These studies should generate important information to guide clinicians and policymakers. In the meantime, parents should know that genetic results sometimes confirm an already suspected dismal prognosis and sometimes yield only ambiguous findings. Anticipatory discussions should try to give parents a realistic understanding of the likely impact of a genetic diagnosis. Both doctors and parents should recognize that the clinical usefulness of diagnostic genomic testing in newborns is a work in progress. We are only a decade into the age of true genomic medicine. We still have much to learn.

The Oriental ratsnake Ptyas mucosa is a common non-venomous snake of the colubrid family, with a wide geographic range spanning much of South and Southeast Asia. P. mucosa is widely cultivated dut to it used in traditional medicine, scientific research, and handicrafts. Therefore, genome resources could play an important role in the efficacy of traditional medicine and the analysis of the living environment of the species. We collected a snake sample in Hezhou, Guangxi, China, which was identified as P. mucosa by morphological identification. Here we present a highly continuous P. mucosa genome with a genome size of 1.74Gb. The scaffold N50 length is 9.57Mb and the maximal length of scaffold is 78.3Mb, the P. mucosa genome has a CG content of 37.9% and the integrity of the gene reached 86.6%.Assembled using long-reads, the total length of the repeat sequence in the genome reached 735 Mb, and its repeat content was as high as 42.19%. A total of 24,869 functional genes were annotated. This study will assist in the understanding of the P. mucosa, and also provide a basis for medicinal research.

The study of the currently known >3,000 species of snakes can provide valuable insights into the evolution of their genomes. Deinagkistrodon acutus, also known as Sharp-nosed Pit Viper, one hundred-pacer viper or five-pacer viper, is a venomous snake with significant economic, medicinal and scientific importance. Widely distributed in southeastern China and South-East Asia, D. acutus has been primarily studied for its venom. Here, we employed next-generation sequencing to assemble and annotate a highly continuous genome of D. acutus. The genome size is 1.46 Gb; its scaffold N50 length is 6.21 Mb, the repeat content is 42.81%, and 24,402 functional genes were annotated. This study helps to further understand and utilize D. acutus and its venom at the genetic level.

Radiotherapy, also known as radiation therapy, is a treatment modality based on the use of high energy rays or radioactive substances, to damage tumoral cells and halt their growth and division. It is an effective tool for treating cancer of different kinds for more than 100 years with remarkable outcomes for cancer patients. This technique is characterised by notable technological innovations and methodologies, enhanced precision and effectiveness. Initially, precision and efficacy of radiotherapy are improved by technological advancements, such as the development of linear accelerators and brachytherapy. As a result, Radiotherapy has transformed the prognosis for cancer patients enhancing survival rates and improving quality of life. Also, it offers targeted and personalized treatment with advancements in imaging techniques such as Intensity-Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT) and innovations like Image-Guided Radiation Therapy (IGRT), Adaptive Radiotherapy (ART) and Artificial Intelligence (AI). Additionally, techniques like proton therapy result in reduced side effects and collateral damage. Although, among the challenges and future perspectives we note the issue of affordability and accessibility. Ongoing research into immunotherapy and nanotechnology and their synergy with radiation therapy shows potential for further improving treatment outcomes. In conclusion, the evolution of radiotherapy has been a transformative journey, reshaping the prognosis and outcomes for cancer patients.

Pea (Pisum sativum L.), like most legumes, forms mutualistic symbioses with nodule bacteria and arbuscular mycorrhizal (AM) fungi. The positive effect of inoculation is partially determined by the plant genotype, thus, pea varieties with high and low symbiotic responsivity have been described, but the molecular genetic basis of this trait remains unknown. Here, we compare the symbiotically responsive breeding line ‘Triumph’ of grain pea with its parental cultivars ‘Vendevil’ (a donor of high symbiotic responsivity) and ‘Classic’ (a donor of agriculturally valuable traits) using genome and transcriptome sequencing. We show that ‘Triumph’ inherited one-fourth of its genome from ‘Vendevil’, including the genes related to AM and nodule formation, and reveal that under combined inoculation with nodule bacteria and AM fungi, ‘Triumph’ and ‘Vendevil’, in contrast to ‘Classic’, demonstrate similar up-regulation of the genes related to solute transport, hormonal regulation and flavonoid biosynthesis in their roots. We also identify the gene PsGLP2, whose expression pattern distinguishing ‘Triumph’ and ‘Vendevil’ from ‘Classic’ correlates with difference within the promoter region sequence, making it a promising marker for the symbiotic responsivity trait. The results of the study may be helpful for future molecular breeding programs aimed at creation of symbiotically responsive cultivars of pea.

The pro-protein convertase FURIN (PCSK3) is implicated in a wide range of normal and pathological biological processes such as infectious disease, cancer and cardiovascular disease. Previously, we performed a systemic inhibition of FURIN in a mouse model of atherosclerosis and demonstrated significant plaque reduction and alterations in macrophage function. To understand the cellular mechanisms affected by FURIN inhibition in myeloid cells, we optimized a CRISPR-mediated gene deletion protocol for successfully deriving hemizygous (HZ) and nullizygous (NZ) FURIN knockout clones in U937 monocytic cells using lipotransfection based procedures and a dual guide RNA delivery strategy. We observed differences in monocyte and macrophage functions involving phagocytosis, lipid accumulation, cell migration, inflammatory gene expression, cytokine release patterns, secreted proteomics (cytokines) and whole-genome transcriptomics between wild-type, HZ and NZ FURIN clones. These studies provide a mechanistic basis on the possible roles of myeloid cell FURIN in cardiovascular disorders.

Malaxidinae is one of the confusing groups with classification in Orchidaceae. Previous phylogenetic analysis reveals that the relationships among the taxa in Malaxidinae have not yet been reliably established using a few plastome regions or nuclear ribosomal internal transcribed spacer (nrITS). In the present study, the complete plastomes of Oberonia integerrima and Crepidium purpureum were assembled using high-throughput sequencing. Combined with publicly available complete plastome data, this resulted in a data set of 19 plastomes, including 17 species of Malaxidinae. The plastome feature and phylogenetic relationship were compared and analyzed. The results showed that: (1) The plastomes of Malaxidinae species possessed the quadripartite structure of typical angiosperms, with sizes ranging from 142,996 bp to 158,787 bp and encoding from 125 to 133 genes. The ndh genes were lost or pseudogenized with varying degrees in six species. An unusal inversion was detected in the Large Single-Copy region (LSC) of Oberonioides microtatantha. (2) A total of 8 regions, including ycf1, matK, rps16, rpl32, ccsA-ndhD, clpP-psbB, trn-FGAA-ndhJ, and trnSGCU-trnGUCC, were identified as mutational hotspots. (3) Based on complete plastomes, 68 protein-coding genes and 51 intergenic regions, respectively, the phylogenetic analyses resolved genera-level relationships in this subtribe with strong support. The Liparis was supported as polyphyletic.

The fungal order Entomophthorales in the Zoopagomycotina includes many fungal pathogens of arthropods. This review explores five genera in the Erynioideae subfamily, namely Erynia, Furia, Pandora, Strongwellsea, and Zoophthora. This is the largest subfamily in the Entomophthorales including 125 described species. The species diversity, global distribution, and host range of this subfamily are summarized, revealing that relatively few taxa are geographically widespread, and few have broad host ranges, contrasting with a large number of species with single reports, from one location and one host species. The insect orders infected by the greatest numbers of species are the Diptera and Hemiptera. Across the subfamily relatively few species have been cultivated in vitro and those that have require more specialized media than any fungi. Given their potential to attack arthropods and in the fungal evolutionary tree, which species might be adopted for biological control purposes or biotechnological innovations are highlighted. Current challenges in the implementation of these species in biotechnology include the limited ability or difficulty in culturing many in vitro, a correlated paucity in genomic resources, and considerations regarding the host ranges of different species.

This comprehensive review traces the transformative journey of genomic mapping, ushering in the era of "Genomic Atlas 2.0," characterized by advanced strategies and cutting-edge technologies. Beginning with a historical overview, it highlights the evolution from early linkage analysis to the current landscape shaped by high-throughput sequencing. Key breakthroughs are emphasized, showcasing the pivotal role of platforms such as Illumina and Oxford Nanopore in accelerating the identification of genetic variations. Long-read sequencing technologies, including PacBio and Oxford Nanopore, are explored as transformative elements overcoming limitations associated with short-read sequencing. The review delves into spatial genomics and chromatin conformation capture techniques, revealing the three-dimensional intricacies of the genome, with a particular focus on the revolutionary impact of Hi-C in understanding chromatin interactions. CRISPR technologies emerge as indispensable tools in Genomic Atlas 2.0, enabling targeted genome editing and the generation of precise genetic models. Functional genomics screens, utilizing RNA interference and CRISPR-based techniques, are discussed for their scalable precision in deciphering genome functions. Navigating challenges, the review addresses complexities in data integration and ethical considerations, offering strategies to ensure the robustness and ethical conduct of genetic mapping. Looking optimistically towards the future, it explores opportunities such as improved sequencing accuracy and novel applications of CRISPR technologies. Envisioning the expansion of genomics into personalized medicine, agriculture, and conservation biology, the review serves as a guiding resource for researchers, scientists, and students navigating the intricate terrain of Genomic Atlas 2.0.

In China, 65 types of venomous snakes exist, with the Chinese Cobra Naja atra being prominent and a major cause of snakebites in humans. Furthermore, N. atra is a protected animal in some areas, as it has been listed as vulnerable by the International Union for Conservation of Nature. Recently, due to the medical value of snake venoms, venomics has experienced growing research interest. In particular, genomic resources are crucial for understanding the molecular mechanisms of venom production. Here, we report a highly continuous genome assembly of N. atra, based on a snake sample from Huangshan, Anhui, China. The size of this genome is 1.67 Gb, while its repeat content constitutes 37.8% of the genome. A total of 26,432 functional genes were annotated. This data provides an essential resource for studying venom production in N. atra. It may also provide guidance for the protection of this species.

We compared the performance of matrix-assisted laser desorption/ionization followed by a time of flight (MALDI-TOF) mass spectrometry and genomic DNA extraction followed by sequencing, assembly, and alignment for phylogenetic assessment (Genomics method). We collected the samples from four contaminated rivers in the Dominican Republic and analyzed MALDI-TOF efficacy and accuracy for identifying bacteria in the samples. We evaluated the results for both methods (MALDI-TOF and Genomics) and reported a similarity percentage between each method's results. The MALDI-TOF method had a 72.41\% of coincidence with the Genomics method. This could have been sequence contamination found in the Genomics method. When it was later filtered, the result's coincidence rate went up to 90\%.

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.

Adamantinomatous Craniopharyngioma (ACP) is a rare epithelial tumor located in the craniopharyngeal duct, often associated with high morbidity and a high long-term recurrence rate. ACP is predominantly diagnosed in children below the age of 15 and accounts for a majority of Craniopharyngioma cases in the United States. It is most commonly caused by a mutation in exon 3 of the CTNNB1 gene, which promotes overaccumulation of β-Catenin in the WNT pathway. As β-Catenin accumulates, it over-activates the transcription factor, causing an over-transcription of WNT proteins and uncontrolled cell growth. Current methods of treatment for ACP are centered around surgical intervention and radiotherapy, including gross-total resection (GTR), subtotal resection (STR), and a combination of subtotal resection and adjuvant radiotherapy (STR+XTR). These methods of treatment are associated with high risk due to the proximity of ACP to critical structures near the craniopharyngeal duct. High recurrence rates and morbidity are closely associated with current methods of treatment and other methods have yet to be attempted in craniopharyngioma. This review will explore two possible methods of non-surgical and non-radiological therapeutic interventions. The use of RNAi therapy and CRISPR may provide insight and be a potential way to treat ACP with increased quality of life and decreased recurrence rates.

The liver is not only a digestive gland, but also an immune tissue that receives a double infusion from the hepatic artery and the hepatic portal vein. Receiving 80% of its blood supply from the intestine through the hepatic portal vein system, the liver is enriched with a large number of innate immune cells, which carry out the process of immune response by detecting pathogens entering the organism through the intestine. The intestine and liver communicate extensively through the bile ducts, portal vein and the somatic circulation, a bidirectional communication known as the intestinal-liver axis. The mammalian gut is considered an important microbial ecosystem. The interplay between the natural immune system and microbes coordinates the physiology of the whole organism, and in specific mammalian lineages, there is a dependency between the host and its associated microbes. To this end, we explored the regulatory mechanisms of natural immunity genes at the genome-wide level. Based on comparative genomics, 1473 bovine natural immunity genes were obtained by collecting the latest reports of human natural immunity genes and updated bovine genomic data for comparison, and a bovine natural immunity gene database was initially constructed to screen and match calf liver natural immunity differential genes mainly affected by the phylum Mimosoidea and the phylum Thick-walled Bacteria, and 16 differentially expressed natural immunity genes were obtained. In addition, the results of IPA analysis indicated that the upstream factor IL-2 initiated the PI3K/AKt/mTOR, mitogen-activated protein kinase (MAPK) pathway and JAK/STAT5 pathway, leading to the liver's involvement in gut microbial immune regulation.

The exploration of three-dimensional (3D) DNA structures marks a pivotal shift in genomics, offering unprecedented insights into the intricacies of cellular regulation, disease genesis, and the potential for novel diagnostic and therapeutic strategies. This study delves into the dynamic nature of 3D genome organization, investigating how these structures influence cellular functions in response to environmental changes and over time. Through a combination of real-time imaging and advanced computational models, we aim to unravel the complex interplay between 3D DNA structures, non-coding RNAs, and chromatin organization, and their collective impact on gene expression and cellular differentiation. A significant focus is placed on understanding the role of 3D DNA structures in the development and progression of genetic disorders. By employing comprehensive genomic and epigenomic profiling, this research seeks to identify structural aberrations linked to diseases, paving the way for the development of targeted diagnostics and therapies. Additionally, the study explores the potential of genome editing technologies, such as CRISPR-Cas systems, in correcting these structural abnormalities, while also addressing the ethical, legal, and social implications (ELSI) of such interventions. Integrating data from various genomic analyses, we propose the development of advanced computational models to predict the effects of 3D DNA structures on gene expression and cellular function. This integrative approach not only promises to enhance our understanding of genomic regulation but also sets the stage for groundbreaking advances in genomics-based diagnostics and therapeutics. The findings of this study have the potential to revolutionize our approach to treating genetic disorders, offering a new frontier in personalized medicine.

Brown-Spotted Pit viper (Protobothrops mucrosquamatus), also known as the Chinese habu, is a widespread and highly venomous snake distributed from from northeastern India to eastern China. Genomics research can help provide much insight in understanding venom components and natural selection in vipers. Here, we collected, sequenced and assembled the genome of a male P. mucrosquamatus individual from China, producing a highly continuous reference genome, with the length of 1.53 Gb and 41.18% repeat element content. From this 24,799 genes were identified, and 97.97% genes could be annotated. Nuclear genome single-copy genes phylogenetic tree including 6 species verified the validity of our genome assembly and annotation process. This research will contribute to further study on Protobothrops biology and the genetic basis of the snake venom.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

Goat milk's medicinal properties and potential cosmetic and health benefits have prompted extensive scientific investigation into its therapeutic applications, particularly for human skin conditions like eczema and psoriasis. Genetic factors, including genes such as lactoferrin (LTF), lysozyme (LYZ), and β-casein (CSN2), play a crucial role in shaping milk composition and its effects on skin health. This review explores the utilization of genomic tools to elucidate the genomic profiles of dairy goat breeds and the medicinal properties of goat milk, particularly in addressing key skin diseases. Genetic determinants of milk composition, quality, nutritional quality, and functional properties such as the growth hormone receptor (GHR), butyrophilin (BTN1A1) and lactoglobulin (LGB) genes, facilitating targeted breeding strategies to enhance the production of bioactive compounds with dermatological relevance have been identified. Future genomic approaches should aim at exploring goat milk's immunomodulatory, antimicrobial, and antioxidant activities, offering potential applications in skin care formulations for managing inflammatory skin conditions. Furthermore, the integration of genomic data with functional studies can provide valuable insights into the therapeutic effects of goat’s milk and its derivatives in addressing skin diseases.

Multiple sequence alignments and phylogenetic trees are rich in biological information and are fundamental to research in biology. PhyKIT is a tool for processing and analyzing the information content of multiple sequence alignments and phylogenetic trees. Here, we describe how to use PhyKIT for diverse analyses, including (i) constructing a phylogenomic supermatrix, (ii) detecting errors in orthology inference, (iii) quantifying biases in phylogenomic data sets, (iv) identifying radiation events or lack of resolution using gene support frequencies, and (v) conducting evolution-based screens to facilitate gene function prediction. Several PhyKIT functions that streamline multiple sequence alignment and phylogenetic processing—such as renaming FASTA entries or tree tips—are also discussed. These protocols demonstrate how simple command-line operations in the unified framework of PhyKIT facilitate diverse phylogenomic data analysis and processing, from supermatrix construction and diagnosis to gene function prediction.

Hemoglobinopathies are a group of disorders in which the hemoglobin molecule has abnormal production or structure. The hemoglobin molecules in red blood cells (RBC) are impacted by the blood disease known as sickle cell disease (SCD), and Thalassemia is one of the major monogenic disorders that reduces hemoglobin production( Kohne et al ., 2011). This disorder results in a large number of red blood cells being destroyed, leading to anemia. India bears a huge burden of hemoglobinopathies; thalassemia is the most prevalent (Mondal SK et al., 2016). A key component of thalassemia prevention is a successful screening procedure to identify Thalassemia carriers. Effective screening programs have numerous obstacles, especially in environments with limited resources. Machine learning (ML) has been used to solve technical and domain-specific problems in a variety of prognostic and diagnostic medical jobs. In this work, we aimed to identify and analyze the most common mutation of β--thalassemia and sickle cell disease from the north Indian population by employing Machine learning-based algorithms. To accurately predict the carrier state from a simple blood test, and to predict pathogenic hemoglobin variants in a group of individuals, these results demonstrate the application of integrated bioinformatics and machine learning approaches. This study contributes to the validation of the models based on data from several individuals and hemoglobinopathies.